There are four interrelated objectives of this research program. The first is to define in a detailed manner the interrelated roles of ions, particularly calcium ion, and cyclic nucleotides in cell activation. In particular, drugs, which either increase or decrease the permeability of biological membranes to calcium, will be employed to define the effects of known changes in calcium uptake upon cell metabolism. To supplement these studies an attempt will be made to develop a general method for measuring changes in calcium ion concentration in the cell cytosol. The cellular systems to be studied include the peripheral lymphocyte, the nucleated and non-nucleated red blood cell, the mast cell, and kidney cells grown in tissue culture. The second objective is to define the cellular basis of vasopressin action on Na ion transport in the toad bladder, and the nature of the metabolic cooperation between mitochondrial-rich and granular cells in the epithelial cell layer of this tissue. The third objective is that of defining the mechanism of steroid hormone actions upon Na ion and Ca 2 ions transport in toad bladder, isolated hepatocytes, and isolated myometrial cells and subcellular fractions from these cell types. The major hypothesis to be explored in this work is that these hormones alter membrane transport functions by altering the phospholipid structure of membranes. The fourth objective is to define, in D-replete animals, those factors that control the metabolism of vitamin D3 and to continue to explore the mode of action of 1,25 (OH)2D3 upon intestinal calcium transport, and the metabolism of isolated intestinal cells.